Prosthetic implant lenses are widely used to replace natural lenses that are affected by cataracts. Cataracts are the leading cause of blindness in the industrialized and developing world. The standard medical procedure for treatment is to remove the natural cloudy lens by elective cataract surgery and replace it with an intra-ocular lens.
Currently, flexible silicone is progressively replacing the classical polymethyl-methacrylate (PMMA) material and its derivative polymers as an intra-ocular lens implant material. Continued perfection of the cataract operation has brought new techniques that remove the natural lens through a self-sealing incision so tiny that no sutures are required. Thin, flexibly foldable implant materials permit the insertion of the implant lens through the same small size self-sealing incision of the cataract operation, which has the important advantage to considerably reduce the risk of post-operative complications.
Except for a preferred requirement of high flexibility, materials for intra-ocular lenses should be clear, highly transparent and should allow for the manufacturing of lenses with high refractive indices. An intra-ocular lens with a high refractive index has the advantage that it can be thinner at the same dioptric power as an intra-ocular lens with lower refractive index.
In order to increase the refractive index of intra-ocular lenses, co-polymers of polysiloxane and polymethacrylates may be prepared. Also, sulphur compounds can be introduced into the siloxane polymer. But despite these modifications, the refractive index of silicone materials is still limited, and a thin lens thereof does not provide much optical power.
It is recognized that the inclusion of diphenyl siloxane or phenyl-methyl siloxane into a polysiloxane results in a polymer of higher refractive index as disclosed in U.S. Pat. No. 3,996,189. Introduction of aromatic groups is now a general approach to increase the refractive index of intra-ocular lens materials while maintaining biocompatibility. Although other refractive index modifying groups such as cyclo-alkyl groups or aromatic groups, optionally combined with phenyl groups (JP2000017176) or phenol groups (U.S. Pat. No. 5,541,278), can also be used, conventional co-polymers for intra-ocular lenses consist of dimethylsiloxane-phenylmethylsiloxane co-polymers or dimethylsiloxane-diphenylsiloxane co-polymers as described in e.g. U.S. Pat. No. 5,147,396, JP10305092, EP 0335312, WO 93/21245, WO 95/17460, U.S. Pat. No. 5,444,106 and U.S. Pat. No. 5,236,970.
Thus, it is generally known that silicone materials with higher refractive index can be obtained by increasing the phenyl content of silicone (co)polymers. At a phenyl content of approximately 15 mole %, a polydimethyl siloxane/methylphenyl siloxane co-polymer has a refractive index of 1.462, (Gu & Zhou, Eur. Polymer J. 34, pp. 1727-33 [1998]). Although certain levels of refractive indices can be attained by using polymers and methods for their production as known in the prior art, there still is a need for materials with which intra-ocular lenses of a wide range of refractive indices, i.e. both high and low, can be produced.
Despite the positive effect on the refractive index, the introduction of refractive index modifying groups, such as phenyl-groups, in polysiloxanes is known to result in several important disadvantages.
A principal disadvantage is associated with the reduced flexibility or elongation of cross-linked networks of such modified polymers. The presence of phenyl groups attached to the alternating silicon-oxygen backbone of the siloxane causes the (co)polymer to become relatively stiff and, despite their potential dioptric power, the suitability of such polymers as a material for intra-ocular lenses is greatly reduced. In general, the introduction of aromatic groups, such as phenyl groups, in polysiloxane increases the glass transition temperature, or Tg, of the polymer, making it more hard and brittle and less flexible over a wider temperature range. This renders the material more vulnerable to cracking or breaking during folding and reduces the suitability of phenylated polysiloxanes as a material for intra-ocular lenses because such lenses must be folded and inserted through a self-sealing incision.
A well-known remedy to the problem of vulnerability to cracking is to reinforce the lens and improve its mechanical properties by combining the polymer with a solid filler material. Mostly, finely powdered silica is used as a filler material for this purpose. This filler material has a refractive index of 1.46. Since differences in the refractive index of the filler material and the polymer are not allowable in an optical lens, the maximum refractive index of a lens containing such filler material is ultimately 1.46.
Therefore, the use of silicone as an intra-ocular lens implant material and particularly the development of silicone with the enhanced material characteristics that would support broadening of such use is determined, at large, by the maximum attainable refractive index of the material and its associated flexibility. In order to obtain higher flexibility, the glass transition temperature of the material must be reduced. One method of reducing the glass transition temperature of phenyl-modified polysiloxanes is to link the phenyl-groups to the silicon-oxygen backbone by alkanediyl-bridges. Such modification of polysiloxanes is known from U.S. Pat. No. 4,780,510 wherein a hydride/vinyl reaction pair is used. U.S. Pat. No. 5,233,007, WO 93/21258 and U.S. Pat. No. 5,420,213 describe a process wherein phenyl groups are introduced in tetramethyl cyclo tetrasiloxane via an addition reaction with styrene to produce a tetramethylstyryl cyclo tetrasiloxane monomer.
However, another disadvantage associated with the introduction of refractive index modifying groups in polysiloxanes is related to the molecular weight of the polymer and the attainable mechanical strength of the polymer network in the silicone material. Polysiloxanes with a high content of phenyl groups generally exhibit a reduced molecular weight and therefore flexibility after crosslinking. This lower molecular weight reduces the mechanical strength of the network after cross-linking of the (co)polymers. In general, styrene-modified polysiloxanes or polysiloxanes with high phenylsiloxane content exhibit lower molecular weights compared to unmodified polysiloxane materials (i.e. with a low refractive index). This results in difficulties with achieving the high levels of flexibility, elasticity and mechanical strength of cross-linked rubbers. It is known, for example, that diphenyl cyclosiloxanes cannot easily be polymerized to high molecular weight polymers as a result of the unfavorable thermodynamics of the reaction from rings to chains (Journal of Polymer Science Part A: Polymer Chemistry, v35(10), p 1973). Only the application of non-equilibrium reaction conditions will yield the desired product, but such conditions are perceived as less suitable for large-scale production.
Thus, the introduction of refractive-index modifying groups in polysiloxanes results in reduced flexibility of the silicone prepared therefrom and in reduced mechanical strength due to the presence of relatively low molecular weight polysiloxanes and reduced flexibility of the polymer chains themselves.
Yet another important factor to consider in preparing polysiloxanes for intra-ocular lens applications relates to the presence of free reactive groups in the final material. The methods as described in U.S. Pat. No. 4,780,510 yield products wherein the presence of free unreacted vinyl groups in the polymer after completion of the addition and cross-linking reaction cannot be avoided nor controlled. This is not useful in intra-ocular lens applications, as it may result in allergy, inflammation or other discomforts in patients.